PET is a medical imaging technique in which a radioactively labeled substance is administered to a patient and then traced within the patient's body by means of an instrument that detects the decay of the isotope. In PET, a chemical tracer compound having a desired biological activity or affinity for a particular organ is labeled with a radioactive isotope that decays by emitting a positron (positive electron). The emitted positron loses most of its kinetic energy after traveling only a few millimeters in living tissue. It is then highly susceptible to interaction with an electron, an event that annihilates both particles. The mass of the two particles is converted into 1.02 million electron volts (1.02 MeV) of energy, divided equally between two 511 keV photons (gamma rays). The two photons are emitted simultaneously and travel in almost exactly opposite directions. The two photons penetrate the surrounding tissue, exit the patient's body, and are absorbed and recorded by photodetectors typically arranged in a circular array.
Biological activity within an organ under investigation can be assessed by tracing the source of the radiation emitted from the patient's body to the photodetectors. The source of the radiation can be accurately estimated by linking each photodetector with several other photodetectors on the opposite side of the photodetector array and registering a signal only if two detectors sense 511 keV photons coincidentally. When a coincidence is registered, an annihilation is recorded along a line connecting the two photodetectors. In this manner, a circumferential array of photodetectors can establish the sources of all coincident pairs of photons that originate within a volume defined by straight lines joining paired detectors. A computer program reconstructs the spatial distribution of the decaying isotopes within the patient. With suitable interpretation, PET images provide a noninvasive, regional assessment of many biochemical processes associated with human organs.
The value of PET as a clinical imaging technique is in large measure dependent upon the performance of the photodetectors. The typical PET camera comprises an array of photodetectors consisting of scintillator crystals coupled to photomultiplier tubes (PMTs). When a photon strikes a detector, it produces light in one of the scintillator crystals that is then sensed by the PMT, which registers the event by passing an electronic signal to the reconstruction processing circuitry. The scintillator crystals themselves must have certain properties, among which are (1) good stopping power, (2) high light yield, and (3) fast decay time.
Stopping power is the ability to stop the 511 keV photons in as little material as possible so as to reduce the overall size of the photodetector, of which the scintillator crystals form a substantial portion. Stopping power is typically expressed as the linear attenuation coefficient (tau) having units of inverse centimeters (cm.sup.-1). After a photon beam has traveled a distance "x" in a crystal, the proportion of photons that have not been stopped by the crystal is calculated as follows: EQU fraction of unstopped photons=e.sup.(-tau * x).
Thus, after traveling a distance of 1/tau (the "absorption length"), approximately 37% of the photons will not have been stopped; 63% will have been stopped. Likewise, 63% of the remaining photons will have been stopped after traveling an additional distance of 1/tau. For PET, one wants 1/tau to be as small as possible so that the photodetector is as compact as possible.
Light yield is also an important property of scintillators. Light yield is sometimes referred to as light output or relative scintillation output, and is typically expressed as the percentage of light output from a crystal exposed to a 511 keV photon beam relative to the light output from a crystal of thallium-doped sodium iodide, NaI(Tl), exposed to a 511 keV photon beam. Accordingly, the light yield for NaI(Tl) is defined as 100.
A third important property of scintillators is decay time. Scintillation decay time, sometimes referred to as the time constant or decay constant, is a measure of the duration of the light pulse emitted by a scintillator, and is typically expressed in units of nanoseconds (nsec). As noted above, in PET, the source of biological activity within an organ under investigation is determined by tracing the source of coincident photons emitted from the patient's body to the photodetectors. When two 511 keV photons are detected at the same time by a pair of photodetectors, the source of the photons is known to lie along the linear path connecting the two photodetectors. In general, only a fraction of the detected photons are in coincidence and thus used in the reconstruction analysis. Moreover, many false coincidences are registered because the finite decay time associated with each scintillator may cause it to emit light at the same time as another scintillator when in fact the photons inducing the light were slightly out of coincidence. For example, a photon arriving at one photodetector may produce a flash of light that does not decay (i.e., "turn off") until after a later photon, not in coincidence, produces a flash of light in a detector on the side opposite the first detector. In this instance, the flashes would overlap, and the photodetectors would register them as in coincidence. Thus, scintillator materials with long decay constants have an inherent problem in detecting coincident photons.
In addition to the problem of false coincidences, the positron emitting tracer compounds themselves typically have very short half-lives. In fact, most medical facilities performing PET also operate on-site accelerators to produce the short-lived radioactively labeled tracer compounds. Because of the short half-lives of these compounds, data on the occurrence of coincident photons needs to be gathered at as high a rate as possible. As noted above, the majority of the detected photons are not in coincidence, i.e.. they are from sources outside the plane of the detector array. Consequently, if a scintillator's decay constant is short, then more of its time will be available for the detection of coincident photons.
In addition to the three important properties discussed above, scintillator crystals for PET should be easy to handle. For example, certain known scintillators are very hygroscopic, i.e., they retain moisture, making it necessary to very tightly encapsulate them to allow their use as scintillators in PET. These hygroscopic scintillators are expensive and difficult to use.
Known scintillator materials include (1) plastic scintillators, (2) thallium-doped sodium iodide (NaI(Tl)), (3) cesium fluoride (CsF), (4) bismuth germanate (Bi.sub.4 Ge.sub.3 O.sub.12, also referred to as "BGO"), and (5) barium fluoride (BaF.sub.2). Of these five scintillators, only the latter two, BGO and BaF.sub.2, are used routinely for PET.
Plastic scintillators, typically composed of polystyrene doped with a wavelength-shifting additive, are commercially available under such trade names as PILOT U and NE 111. Upon excitation with a 511 keV photon, plastic scintillators emit a light pulse having a very fast decay constant of approximately 1.5 nsec and light output proportional to the energy of the incident photon. The main disadvantage of plastic scintillators is their low density (approximately 1.1 to 1.2 g/cm.sup.3) due to the light atoms (hydrogen and carbon) that make up the molecules of the material. Because of their low density, plastic scintillators have poor stopping power, and are therefore poorly suited for use in PET.
NaI(Tl), thallium-doped sodium iodide, has the best light output of the five scintillators listed above. NaI(Tl) also has reasonably good stopping power 1/tau=3.0 cm at 511 keV). However, NaI(Tl) has a long decay constant (250 nsec), a significant disadvantage for use in PET. NaI(Tl) has an additional disadvantage: it is highly hygroscopic, making it extremely difficult to handle in that it must be tightly encapsulated in bulky cans.
CsF, cesium fluoride, has an advantage over plastic scintillators because of its relatively high density (4.61 g/cm.sup.3) and consequent stopping power. However, the light output and decay constant of CsF are inferior to those of plastic scintillators. CsF is also highly hygroscopic, well above NaI(Tl) which, as noted above, makes it expensive and difficult to handle.
BGO has the highest density (7.13 g/cm.sup.3) of the five known scintillator materials listed above. Its stopping power is the best of the five materials (1/tau=1.1 cm at 511 keV). As a result, BGO is best able to absorb 511 keV photons efficiently in small crystals. However, BGO's very long delay constant (300 nsec), longer even than NaI(Tl), is a significant disadvantage for use in PET.
The use of BaF.sub.2 as a scintillator material is described in Allemand et al. U.S. Pat. No. 4,510,394. BaF.sub.2 emits light having two components: a slow component having a decay constant of approximately 620 nsec and a fast component having a decay constant of approximately 0.6 nsec. BaF.sub.2 has a light yield of approximately 16% that of NaI(Tl) and about half the stopping power of BGO 1/tau=2.3 cm at 511 keV). Unlike CsF and NaI(Tl), BaF.sub.2 is not hygroscopic.
The fast component of BaF.sub.2 emits light in the ultraviolet region of the spectrum. Glass photomultiplier tubes are rat transparent to ultraviolet light, so a quartz photomultiplier tube must instead be used to detect the fast component of BaF.sub.2. Since quartz photomultiplier tubes are substantially more expensive than glass, one would prefer to avoid using BaF.sub.2, if possible, in favor of using a scintillator that can be detected by a glass photomultiplier tube. The fast component gives BaF.sub.2 very good timing resolution, but the slow component limits its high rate capabilities. In other words, it takes longer for BaF.sub.2 to get ready for the next event.
Of the known scintillator materials, BGO has the best stopping power, NaI(Tl) has the best light yield, and BaF.sub.2 has the best timing resolution. However, as noted above, some of these materials have significant shortcomings which hinder their performance as scintillators for PET: BGO has a very long decay constant; NaI(Tl) also has a very long decay constant and is hygroscopic. Of these materials, BaF.sub.2 has the best balance of stopping power, light output and decay constant, and does not present a problem with hygroscopy. However, the slow component of BaF.sub.2 does limit its race capabilities.